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Objective To screen differentially expressed microRNAs(miRNAs)in plasma exosomes of active rheumatoid arthritis(RA)patients and healthy controls and conduct bioinformatics analysis for exploring the role and potential clinical application value of miRNAs in the pathogenesis of RA.Methods From January 2023 to April 2023,39 RA patients who visited the Rheumatology and Immunology Department of the Second Affiliated Hospital of Soochow University were selected as the study subjects,while 39 healthy individuals were selected as normal controls.The expression levels of miRNAs in plasma exosomes were detected by Illumina high-throughput sequencing technology,and the differentially expressed miRNAs were obtained by log2(Fold Change)absolute value>1 and P value<0.05.Six miRNAs were selected by the order from small to large P-value for bioinformatics analysis and validated using quantitative real-time fluorescence PCR(qRT-PCR).Results Compared with healthy controls,22 aberrantly expressed miRNAs were detected in plasma exosomes of RA patients,of which 4 were up-regulated and 18 were down-regulated.Among them,miR-30b-5p,miR-144-3p,miR-20a-5p,miR-223-5p,miR-425-3p,and miR-589-5p showed changed significantly.GO and KEGG enrichment analysis indicated that differentially expressed miRNAs may be involved in disease progression through regulation of signaling pathways such as TGF-β and PI3K/AKT,which were related to biological processes such as Th17 differentiation,intercellular interactions,and protein phosphorylation.The qRT-PCR validation results showed that the expression of miR-144-3p and miR-425-3p were significantly reduced in plasma exosomes of RA patients compared to healthy controls(t=3.617,3.595,all P<0.001),while the differences of miR-30b-5p,miR-223-5p,miR-589-5p,and miR-20a-5p expression were not statistically significant(t=1.956,1.331,1.662,1.861,all P>0.05).Conclusion The expression profile of plasma exosomal miRNAs changed in RA patients,which may be involved in disease progression through TGF-β and other signaling pathways.Exosome-derived miR-144-3p and miR-425-3p may be potential serological markers for RA diagnosis.
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OBJECTIVE@#To investigate the treatment outcome of laparoscopic partial nephrectomy in the patients with renal tumors of moderate to high complexity (R.E.N.A.L. score 7-10).@*METHODS@#In the study, 186 patients with a renal score of 7-10 renal tumors who underwent laparoscopic partial nephrectomy in Peking University Third Hospital from February 2016 to April 2021 were selected. Laparoscopic partial nephrectomy was performed after examination. The patients were followed-up, and their postoperative hemoglobin, creatinine, complications, and length of hospital stay recorded. The data were represented by mean±standard deviation or median (range).@*RESULTS@#There were 128 males and 58 females in this group, aged (54.6±12.8) years, with body mass index of (25.4 ± 3.4) kg/m2; The tumors were located in 95 cases on the left and 91 cases on the right, with maximum diameter of (3.1±1.2) cm. The patient's preoperative hemoglobin was (142.9±15.8) g/L, and blood creatinine was 78 μmol/L (47-149 μmol/L). According to preoperative CT images, the R.E.N.A.L. score was 7 points for 43 cases, 8 points for 67 cases, 9 points for 53 cases, and 10 points for 23 cases. All the ope-rations were successfully completed, with 12 cases converted to open surgery. The operation time was 150 minutes (69-403 minutes), the warm ischemic time was 25 minutes (3-60 minutes), and the blood loss was 30 mL (5-1 500 mL). There were 9 cases of blood transfusions, with a transfusion volume of 800 mL (200-1 200 mL). Postoperative hemoglobin was (126.2±17.0) g/L. The preoperative crea-tinine was 78 μmol/L (47-149 μmol/L), the postoperative creatinine was 83.5 μmol/L (35-236 μmol/L), the hospital stay was 6 days (3-26 days), and surgical results achieved "the trifecta" in 87 cases (46.8%). In the study, 167 cases were followed up for 12 months (1-62 months), including 1 case with recurrence and metastasis, 4 cases with metastasis, and 2 cases with other tumors (1 case died).@*CONCLUSION@#Laparoscopic partial nephrectomy is safe and effective in the treatment of renal tumors with R.E.N.A.L. score of 7-10. Based on the complexity of the tumor, with the increase of difficulty, the warm ischemia time and operation time tend to increase gradually, while "the trifecta" rate gradually decreases. The complications of this operation are less, and the purpose of preserving renal function to the greatest extent is achieved.
الموضوعات
Male , Female , Humans , Creatinine , Retrospective Studies , Kidney Neoplasms/pathology , Nephrectomy/methods , Treatment Outcome , Laparoscopy , Hemoglobinsالملخص
Objective:To evaluate whether early enteral nutrition could benefit patients with different degrees of shock by dynamic changes of intestinal biomarkers intestinal fatty acid-binding protein (I-FABP) and citrulline.Methods:(1) From February 2021 to February 2023, 133 target patients in the Intensive Care Unit of Suzhou Hospital Affiliated to Nanjing Medical University were enrolled. The observation period was 7 days after admission, and intestinal biomarkers were monitored three times: 24 hours after admission (D1), the third day after admission (D3), and the seventh day after admission (D7). (2) The enrolled patients were divided into two groups according to the dose of norepinephrine received within 48 hours after admission: safe dose group [receiving norepinephrine < 0.3 μg/(kg·min)] and hazardous dose group [receiving norepinephrine ≥0.3 μg/(kg·min)]. The safe dose group was given early enteral nutrition according to the guidelines, and the dangerous dose group was randomly (random number) given early enteral nutrition (EEN) and delayed enteral nutrition (DEN).(4)The dynamic changes of intestinal fatty acid binding protein and citrulline in three groups were observed; The differences of intestinal biomarkers at different time points of dangerous dose of EEN/DEN were compared. The survival time of EEN/DEN group within 28 days was recorded, and Kaplan-Meier survival curve was drawn. Univariate and multivariate regression analyses of 28-day mortality were performed for the included population.Results:(1) The baseline data, APACHEⅡ score, arterial blood lactic acid, AGI grade, feeding interruption, total feeding time within 7 days, and 28-day survival number were statistically different between safe dose EEN group and hazardous dose EEN group ( P < 0.05). Compared the baseline data of the dangerous dose EEN group and the dangerous dose DEN group, only the number of feeding interruptions was statistically different ( P < 0.05). (2) The trend of change in the safe dose EEN group was the same as that in the dangerous dose DEN group: I-FABP decreased significantly from D3 to D7 ( P < 0.05); Citrulline decreased from D1 to D3, but increased from D3 to D7 ( P < 0.05). In dangerous dose EEN group, I-FABP had no significant change during the monitoring period ( P > 0.05). Citrulline decreased significantly from D1 to D3 ( P < 0.05). The EEN/DEN ratio at dangerous dose was significantly different only for D7-I-FABP ( P < 0.05). Compared with the survival curve of EEN/DEN at risk dose, DEN could improve the early survival rate of critically ill patients at risk dose (Breslow test P = 0.0447). (4) Age( OR=1.069,95% CI: 1.002-1.140, P=0.044) was independent risk factor for 28-day death . BMI ( OR= 0.772, 95% CI: 0.604-0.987, P=0.039), no feeding interruption ( OR=0.044,95% CI: 0.004-0.455, P=0.009), total feeding time within 7 days ( OR=0.959, 95% CI: 0.923-0.997, P=0.036) were the protective factors. Conclusions:EEN at the safe dose and DEN at the dangerous dose can effectively reverse the necrosis of enterocyte and promote the recovery of enterocyte function. EEN is not a clear risk factor for death at 28 days, but it not only increases the incidence of feeding interruption, but also do not conduct the recovery of intestinal cell function from the perspective of intestinal biomarkers.
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The main components and working principle of the fluid infusion and blood transfusion warmer were introduced,and the causes for the adverse events of the warmer were summarized based on National Medical Device Adverse Event Monitoring Information System and related literature in the world.The potential risks of the warmer were analyzed during operation,and the quality concerns and corresponding evaluation methods were proposed for the warmer from the aspects of device marking and documentation,structure,and temperature.References were provided for standard preparation,pre-market technical review and system verification of the fluid infusion and blood transfusion warmer.[Chinese Medical Equipment Journal,2023,44(10):76-80]
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Objective:To construct a risk prediction model for infection with Klebsiella pneumonia (KP) for patients with severe acute pancreatitis (SAP).Methods:Retrospective analysis was done on the clinical data of 109 SAP patients who were admitted to Shanghai General Hospital, between March 2016 and December 2021. Patients were classified into infection group ( n=25) and non-infection group ( n=84) based on the presence or absence of KP infection, and the clinical characteristics of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) algorithm was used to reduce the dimension of the variables with statistical significance in univariate analysis. A nomogram prediction model was created by incorporating the optimized features from the LASSO regression model into the multivariate logistic regression analysis. Receiver operating characteristic curve (ROC) was drawn and the area under curve (AUC) was calculated; and consistency index (C-index) were used to assess the prediction model's diagnostic ability. Results:A total of 25 strains of KP were isolated from 109 patients with SAP, of which 21(84.0%) had multi-drug resistance. 20 risk factors (SOFA score, APACHEⅡ score, Ranson score, MCTSI score, mechanical ventilation time, fasting time, duration of indwelling of the peritoneal drainage tube, duration of deep vein indwelling, number of invasive procedures, without or with surgical intervention, without or with endoscopic retrograde cholangiopancreatography (ERCP), types of high-level antibiotics used, digestion disorders, abnormalities in blood coagulation, metabolic acidosis, pancreatic necrosis, intra-abdominal hemorrhage, intra-abdominal hypertension, length of ICU stay and total length of hospital stay) were found to be associated with KP infection in SAP patients by univariate analysis. The four variables (APACHEⅡ score, duration of indwelling of the peritoneal drainage tube, types of high-level antibiotics used, and total length of hospital stay) were extracted after reduced by LASSO regression. These four variables were found to be risk factors for KP infection in SAP patients by multiple logistic regression analysis (all P value <0.05). Nomogram prediction model for KP infection in SAP was established based on the four variables above. The verification results of the model showed that the C-index of the model was 0.939, and the AUC was 0.939 (95% CI 0.888-0.991), indicating that the nomogram model had relatively accurate prediction ability. Conclusions:This prediction model establishes integrated the basic clinical data of patients, which could facilitate the risk prediction for KP infection in patients with SAP and thus help to formulate better therapeutic plans for patients.
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OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.
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【Objective】 To investigate the clinical characteristics and treatment strategy of giant multilocular prostatic cystadenoma(GMPC). 【Methods】 The clinical data of a GMPC patient treated in our hospital in July 2021 were retrospectively analyzed. The patient was 73 years old. The clinical manifestations were urgent urination and frequent urination. The prostate specific antigen (PSA) increased slightly. MRI showed giant cystic solid space occupying lesion of the prostate. Domestic and foreign cases of prostate cystadenoma from 2000 to 2021 were retrieved for literature review. 【Results】 Transabdominal laparoscopic radical prostatectomy was performed successfully. The postoperative pathological diagnosis was GMPC. Two weeks after operation, the urinary catheter was removed, and there was no discomfort such as urinary frequency or urinary incontinence. After follow-up for more than 8 months, there was no tumor recurrence or metastasis. 【Conclusion】 There are still some disputes about the oncological characteristics and diagnosis and treatment of GMPC, and there is a lack of long-term follow-up results. Laparoscopic prostatectomy is safe and feasible. Most patients have a good prognosis after surgical treatment. It is necessary to formulate an individualized standard treatment plan based on surgery combined with different patients’ conditions to actively improve the prognosis.
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The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.
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Humans , Mice , Animals , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Acrylamides/pharmacology , ErbB Receptors/metabolism , Cell Line, Tumor , CD47 Antigen/therapeutic useالملخص
Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.
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Prostate cancer (PCa) is a pernicious tumor with high heterogeneity, which creates a conundrum for making a precise diagnosis and choosing an optimal treatment approach. Multiparametric magnetic resonance imaging (mp-MRI) with anatomical and functional sequences has evolved as a routine and significant paradigm for the detection and characterization of PCa. Moreover, using radiomics to extract quantitative data has emerged as a promising field due to the rapid growth of artificial intelligence (AI) and image data processing. Radiomics acquires novel imaging biomarkers by extracting imaging signatures and establishes models for precise evaluation. Radiomics models provide a reliable and noninvasive alternative to aid in precision medicine, demonstrating advantages over traditional models based on clinicopathological parameters. The purpose of this review is to provide an overview of related studies of radiomics in PCa, specifically around the development and validation of radiomics models using MRI-derived image features. The current landscape of the literature, focusing mainly on PCa detection, aggressiveness, and prognosis evaluation, is reviewed and summarized. Rather than studies that exclusively focus on image biomarker identification and method optimization, models with high potential for universal clinical implementation are identified. Furthermore, we delve deeper into the critical concerns that can be addressed by different models and the obstacles that may arise in a clinical scenario. This review will encourage researchers to design models based on actual clinical needs, as well as assist urologists in gaining a better understanding of the promising results yielded by radiomics.
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Male , Humans , Artificial Intelligence , Magnetic Resonance Imaging/methods , Prostatic Neoplasms/diagnostic imaging , Image Processing, Computer-Assisted/methods , Precision Medicine , Retrospective Studiesالملخص
OBJECTIVE@#To delineate the origin and content of a mosaicism small supernumerary marker chromosome (sSMC) in a fetus with combined chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH).@*METHODS@#The fetus of a 31-year-old pregnant woman who had presented at the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City in 2022 was selected as the study subject. Non-invasive prenatal testing suggested that the fetus has harbored a 8.75 Mb duplication in 4q12q13.1. With informed consent, amniotic fluid and peripheral blood samples were taken from the couple for chromosomal karyotyping analysis. The origin and content of a sSMC was identified by CMA, and its proportion in amniotic fluid was determined with a FISH assay.@*RESULTS@#The karyotypes of the pregnant woman, her husband and the fetus were respectively determined as 46,XX, 46,XY,inv(9)(p12q12), and 47,XY,inv(9)(p12q12)pat,+mar[75]/ 46,XY,inv(9)(p12q12)pat[25]. CMA test of the amniotic fluid sample was arr[hg19]4p11q13.1(48978053_63145931)×3, which revealed no mosaicism. However, FISH analysis showed that 59% of interphase cells from the cultured amniotic fluid sample had contained three signals for the centromere of chromosome 4, whilst 65% of interphase cells from the re-sampled amniotic fluid had three such signals, which confirmed the existence of trisomy 8 mosaicism.@*CONCLUSION@#Chromosomal structural abnormality combined with mosaicism can be delineated with combined chromosomal karyotyping and molecular techniques such as FISH and CMA, which has enabled more accurate counseling for the family.
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Humans , Child , Female , Pregnancy , Adult , In Situ Hybridization, Fluorescence , Mosaicism , Genetic Techniques , Amniotic Fluid , Chromosomes, Human, Pair 4الملخص
OBJECTIVE@#To investigate whether dynamic monitoring of citrulline (Cit) has guiding value for early enteral nutrition (EN) in patients with severe gastrointestinal injury.@*METHODS@#A observational study was conducted. A total of 76 patients with severe gastrointestinal injury admitted to different intensive care units of Suzhou Hospital Affiliated to Nanjing Medical University from February 2021 to June 2022 were enrolled. Early EN was performed in 24-48 hours after admission as recommended by the guidelines. Those who did not terminate EN after 7 days were enrolled in the early EN success group, and those who terminated EN within 7 days due to persistent feeding intolerance or deterioration of general condition were enrolled in the early EN failure group. There was no intervention during the treatment. Serum Cit levels were measured by mass spectrometry at admission, before EN starting and EN 24 hours, respectively, and the changes in Cit within EN 24 hours (ΔCit) were calculated (ΔCit = EN 24-hour Cit-Cit before EN starting). Receiver operator characteristic curve (ROC curve) was plotted to investigate the predictive value of ΔCit for early EN failure, and the optimal predictive value was calculated. Multivariate unconditional Logistic regression was used to analyze the independent risk factors for early EN failure and death at 28 days.@*RESULTS@#Seventy-six patients were enrolled in the final analysis, of which 40 succeeded in early EN and 36 failed. There were significant differences in age, main diagnosis, acute physiology and chronic health evaluation II (APACHE II) score at admission, blood lactic acid (Lac) before EN initiation and ΔCit between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 0.929, 95% confidence interval (95%CI) was 0.874-0.988, P = 0.018], ΔCit (OR = 2.026, 95%CI was 1.322-3.114, P = 0.001) and increased feeding rate within 48 hours (OR = 13.719, 95%CI was 1.795-104.851, P = 0.012) were independent risk factors for early EN failure in patients with severe gastrointestinal injury. ROC curve analysis showed that ΔCit had a good predictive value for early EN failure in patients with severe gastrointestinal injury [area under the ROC curve (AUC) = 0.787, 95%CI was 0.686-0.887, P < 0.001], and the optimal predictive value of ΔCit was 0.74 μmol/L (sensitivity was 65.0%, specificity was 75.0%). Combined with the optimal predictive value of ΔCit, "overfeeding" was defined as ΔCit < 0.74 μmol/L and increased feeding within 48 hours. Multivariate Logistic regression analysis showed that age (OR = 0.825, 95%CI was 0.732-0.930, P = 0.002), APACHE II score (OR = 0.696, 95%CI was 0.518-0.936, P = 0.017) and early EN failure (OR = 181.803, 95%CI was 3.916-8 439.606, P = 0.008) were independent risk factors for 28-day death in patients with severe gastrointestinal injury. The new variable "overfeeding" was also associated with an increased risk of death at 28 days (OR = 27.816, 95%CI was 1.023-755.996, P = 0.048).@*CONCLUSIONS@#Dynamic monitoring of Cit has guiding value for early EN in patients with severe gastrointestinal injury.
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Humans , Infant, Newborn , Enteral Nutrition , Citrulline , APACHE , Abdominal Injuries , Cognition , Thoracic Injuriesالملخص
Described as a "don't eat me" signal, CD47 becomes a vital immune checkpoint in cancer. Its interaction with signal regulatory protein alpha (SIRPα) prevents macrophage phagocytosis. In recent years, a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect. Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies, indicating the combination strategy as a general trend of the future. In this review, clinical and preclinical cases about the current combination strategies targeting CD47 are collected, their underlying mechanisms of action are discussed, and ideas from future perspectives are shared.
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OBJECTIVES@#To calculate the likelihood ratios of incest cases using identity by descent (IBD) patterns.@*METHODS@#The unique IBD pattern was formed by denoting the alleles from the members in a pedigree with a same digital. The probability of each IBD pattern was obtained by multiplying the prior probability by the frequency of non-IBD alleles. The pedigree likelihoods of incest cases under different hypotheses were obtained by summing all IBD pattern probabilities, and the likelihood ratio(LR) was calculated by comparing the likelihoods of different pedigrees.@*RESULTS@#The IBD patterns and the formulae of calculating LR for father-daughter incest and brother-sister incest were obtained.@*CONCLUSIONS@#The calculations of LR for incest cases were illustrated based on IBD patterns.
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Male , Humans , Incest , Siblings , Probabilityالملخص
The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.
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Objective:To analyze the indications for prenatal diagnosis and summarize the pregnancy outcomes and its influencing factors of pregnant women with fetal sex chromosome aneuploidy (SCA).Methods:This study retrospectively enrolled 1 372 fetuses prenatally diagnosed with SCA in Medical Genetics Center of Guangdong Women and Children Hospital from January 2013 to December 2021. The relationship between prenatal diagnosis indications and SCA as well as between ultrasound abnormalities, pregnancy outcomes and SCA types were analyzed by Chi-square test and trend Chi-square test. Results:The most common prenatal diagnosis indication was abnormal non-invasive prenatal testing (NIPT) (61.6%, 845/1 372). The most common SCA type was 47,XXY in cases with indications of abnormal NIPT and advanced maternal age, mosaic in cases with high or borderline risk of Down syndrome, and 45,X in cases with increased nuchal translucency or cystic hygroma. Of 1 372 pregnant women with fetal SCA, 17 were lost to follow-up, seven had intrauterine fetal death, and 1 348 (98.3%) were followed up for pregnancy outcomes including 36.3% (489/1 348) continued pregnancies and 63.7% (859/1 348) terminations. Pregnancy termination rates decreased sequentially in pregnant women carrying fetuses with 45,X, 47,XXY, mosaic, 47,XXX and 47,XYY [99.2% (247/249), 74.5% (307/412), 67.8% (156/230), 36.6% (86/235) and 28.4% (63/222), χ2trend=352.76, P<0.001]. There was no significant difference in pregnancy termination rates among the cases with different mosaic mutations (all P>0.05). The pregnancy termination rate was higher in fetuses with SCA complicated by ultrasound structural abnormalities than in those without ultrasound abnormalities and those with ultrasound soft markers [91.5% (182/199) vs 57.1% (535/937) and 67.0% (142/212), χ2 were 83.68 and 36.85, both P<0.001]. Moreover, the pregnancy termination rate in fetuses with SCA complicated by ultrasound soft markers was higher than those without ultrasound abnormalities ( χ2=7.13, P<0.05). Conclusions:NIPT abnormality is the most common indication for prenatal diagnosis of SCA. The types of SCA and ultrasound findings are important factors determining whether the pregnancy would be continued or not.
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The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that " dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.
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Objective:To investigate the effect of SKF96365, store-operated calcium entry (SOCE) inhibitor, on liver and kidney injury induced by paraquat (PQ).Methods:A549 cells were cultured in vitro and divided into the control group (DMSO group, SKF 2 μmol/L group, and SKF 10 μmol/L group) and PQ group (PQ+DMSO group, PQ+SKF 2 μmol/L group, and PQ+SKF 10 μmol/L group). The nuclear factor of activated T cells (NFAT) in A549 cells was detected by luciferase reporter gene technique. The mouse model of PQ poisoning was constructed and divided into the control group, SKF group, PQ group and PQ+SKF group. In the PQ group, mice were injected with 50 mg/kg PQ intraperitoneally; in the SKF group, mice were injected intraperitoneally with 10 mg/kg SKF96365 for 3 days. Mice in the PQ+SKF group received 50 mg/kg intraperitoneal injection of PQ once and 10 mg/kg intraperitoneal injection of SKF96365 daily for 3 days. On the fourth day, the mice were sacrificed, and the liver and kidney tissues were taken. The histopathological changes of liver and kidney tissues were observed by hematoxylin-eosin (H&E) staining, and the apoptosis of liver and kidney tissues was observed by TUNEL staining. One-way analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between groups were performed using the least significant difference t-test. Results:The luciferase reporter gene technology showed that NFAT was significantly activated in the PQ group. After pretreatment with SKF96365, NFAT activation decreased sharply in a dose-dependent manner. HE staining showed that the outline structure of liver and kidney tissues in the PQ groups were unclear, cells swelled and a large number of inflammatory cells infiltrated; in the PQ+SKF group, liver cell swelling and inflammatory cell infiltration decreased significantly. TUNEL staining showed that the apoptotic cells in liver and kidney tissues increased in the PQ groups, and the apoptosis decreased remarkably in the PQ+SKF group.Conclusions:SOCE inhibitor SKF96365 can significantly reduce the liver and kidney injury caused by PQ.
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Objective:To investigate the clinical efficacy of gradual decompression in the treatment of severe traumatic brain injury and its effects on the improvement of intracranial pressure.Methods:The clinical data of 120 patients with severe traumatic brain injury who received treatment in the General Hospital of Taiyuan Iron and Steel (Group) Co., Ltd. from January 2015 to January 2020 were retrospectively analyzed. The included patients were divided into decompressive craniectomy group (control group, n = 64) and gradual decompression group ( n = 56). Intracranial pressure was compared between the two groups at different time points (before surgery, during the surgery, immediately after surgery, 3 and 6 months after surgery). The patient's self-care ability, coma degree, and neurological deficits pre-surgery and 6 months after surgery were evaluated in each group. The incidence of complications throughout the surgery and within 6 months after surgery was calculated to evaluate the quality of life. Results:There was no significant difference in intracranial pressure pre-surgery between the two groups ( P > 0.05). Intracranial pressure in the gradual decompression group was (30.74 ± 2.51) mmHg, (25.11 ± 2.06) mmHg, (21.34 ± 2.01) mmHg, and (16.74 ± 1.54) mmHg respectively during the surgery, immediately after surgery, and 3 and 6 months after surgery, which was significantly lower than that in the control group [(34.31 ± 3.06) mmHg, (30.64 ± 2.57) mmHg, (26.33 ± 2.35) mmHg, (22.64 ± 1.95) mmHg, t = 12.88, 19.03, 12.40, 18.20, all P < 0.001]. There were no significant differences in scores of the Modified Barthel Index (MBI), the Glasgow Coma Scale (GCS), the National Institutes of Health Stroke Scale (NIHSS) pre-surgery between the two groups (all P > 0.05). At 6 months after surgery, the MBI and GCS scores increased and the NIHSS score decreased in each group. There were significant differences in the NIHSS, MBI, and GCS scores between the two groups ( t = 7.61, 6.26, 13.07, all P < 0.001). During the surgery and 6 months after surgery, the incidences of cerebral infarction, delayed cerebral hematoma, and acute encephalocele were significantly lower in the gradual decompression group than in the control group ( χ2 = 4.23, 4.35, 4.83, all P < 0.05). The Generic Quality of Life Inventory-74 Questionnaire scores in environment, psychological health, social relationship, and psychological health domains were significantly higher in the gradual decompression group than in the control group ( t = 8.16, 9.80, 8.68, 7.76, all P < 0.001) Conclusion:This study is the first to analyze the feasibility of gradual decompression for the treatment of severe traumatic brain injury in terms of intracranial pressure, quality of life, and short- and medium-term complications. Findings from this study confirm that gradual decompression can effectively lower intracranial pressure of patients with severe traumatic brain injury, improve neurological function, reduce complications, and improve patients' self-care ability and quality of life.
الملخص
Objective:To establish a prediction model of acute upper gastrointestinal rebleeding (AUGIRB) for elderly patients by combining and applying multiple indicators.Methods:A retrospective observational study was conducted. The clinical data of 161 elderly patients (age ≥ 65 years old) who suffered from acute upper gastrointestinal bleeding (AUGIB) and who were hospitalized in Shanghai General Hospital from July 2018 to December 2020 were recorded. The patients were divided into the rebleeding group (31 cases) and the non-rebleeding group (130 cases) according to whether gastrointestinal rebleeding occurred. Univariate analysis was adopted to screen AUGIRB-related risk factors and Logistic regression analysis was used to screen independent predictors of AUGIRB so that a predictive model was constructed. Based on the area under the curve (AUC) of the receiver operator characteristic curve (ROC curve), the predictive ability of the prediction model for AUGIRB was evaluated, the optimal cut-off value was determined, and the odds ratio ( OR) and its 95% confidence interval (95% CI) were calculated. Bootstrap resampling technology was used to validate the predictive ability of the model. Results:Univariate Logistic analysis showed that oral anticoagulant drugs, oral antiplatelet drugs, albumin (ALB), platelet count (PLT), Glasgow-Blatchford bleeding score (GBS), D-dimer, fibrinogen (FIB), and international normalized ratio (INR) all had a significant effect on the occurrence of AUGIRB among elderly patients. Multivariate Logistic regression analysis showed that the oral antiplatelet drugs ( OR = 11.150, 95% CI was 1.888-65.852, P < 0.05) and GBS score ( OR = 2.503, 95% CI was 1.523-4.114, P < 0.05) were the independent risk factors of AUGIRB among elderly patients, while the ALB ( OR = 0.764, 95% CI was 0.626-0.932, P < 0.05) and FIB ( OR = 0.065, 95% CI was 0.011-0.370, P < 0.05) were the protective factors of AUGIRB among elderly patients. The AUC of the above four indexes joint prediction model was 0.979. The verification results of the model showed that the consistency index (C-index) of the model was 0.986. Conclusion:The prediction model fitted in this research has a high prediction accuracy and it also has a certain reference value for the judgment of elderly patients who suffer from AUGIRB.